title: Guanylated polymethacrylates: a class of potent antimicrobial polymers with low hemolytic activity.
abstract: We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.
authors.affiliation: CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, Victoria 3168, Australia.
authors.forename: Katherine E S
authors.initials: KE
authors.lastname: Locock
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Michl
authors.forename: Jules D P
authors.initials: JD
authors.lastname: Valentin
authors.forename: Krasimir
authors.initials: K
authors.lastname: Vasilev
authors.forename: John D
authors.initials: JD
authors.lastname: Hayball
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Griesser
authors.forename: Laurence
authors.initials: L
authors.lastname: Meagher
authors.forename: Matthias
authors.initials: M
authors.lastname: Haeussler
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006146:Guanidines / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D006146:Guanidines; D011109:Polymethacrylic Acids